Effects of Melatonin on Fat Graft Retention Through Browning of Adipose Tissue and Alternative Macrophage Polarization

Background: Melatonin is a widely used drug that can affect adipocyte inflammation, resulting in adipose tissue browning. Inducing the browning of white fat and changing the inflammatory microenvironment of early transplanted fat have positive effects on the retention rate of fat grafts. This study aimed to evaluate the effects of melatonin on fat graft retention, determine whether it is related to adipose tissue browning and the inflammatory microenvironment, and explore the underlying mechanisms.

Methods: A C57BL/6 mice fat transplantation model was established. The mice were divided into a control group (ethanol), a high-dose group (40 mg/kg/day melatonin), a medium-dose group (20 mg/kg/day melatonin), and a low-dose group (10 mg/kg/day melatonin). They were also given oral gavage treatment for 2 weeks. The grafted fat was collected 2, 4, and 12 weeks after treatment.

Results: The medium-dose and high-dose melatonin groups had significantly higher fat graft retention rates than the control group at 12 weeks. The medium-dose melatonin group had smaller multilocular adipocytes, which enhanced the expression of uncoupling protein 1 and increased neovascularization in the grafted fat. The medium-dose group also had a higher distribution of M2 macrophages.

Conclusions: These findings suggest that melatonin administration can improve the retention of fat grafts through polarization of macrophages toward the anti-inflammatory type and induction of adipose tissue browning.

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